Benlalam Houssem, Vignard Virginie, Khammari Amir, Bonnin Annabelle, Godet Yann, Pandolfino Marie-Christine, Jotereau Francine, Dreno Brigitte, Labarrière Nathalie
INSERM U601, 9 quai Moncousu, 44093, Nantes Cedex 1, France.
Cancer Immunol Immunother. 2007 Apr;56(4):515-26. doi: 10.1007/s00262-006-0204-0. Epub 2006 Jul 28.
Adoptive therapy of cancer has been mostly tested in advanced cancer patients using tumor-infiltrating lymphocytes (TIL). Following discouraging results likely due to poor tumor-specificity of TIL and/or high tumor burden, recent studies reiterate the enormous potential of this therapy, particularly in melanoma. We had performed a phase II/III randomised trial on 88 stage III melanoma patients, who received autologous TIL plus IL-2 or IL-2 alone, after complete tumour resection. We reported previously clinical and immunological results supporting the ability of tumor reactive TIL infusion to prevent further development of the melanoma disease and to increase overall survival of patients bearing only one tumor invaded lymph node. The absence of correlation between overall and disease-free survival and the amount of infused tumor-specific TIL suggested that therapeutic efficiency might depend on other parameters such as antigen specificity, function or persistence of TIL. Here we studied the recognition of a panel of 38 shared tumor-associated antigens (TAA) by TIL infused to the patients included in this assay, in order to determine if treatment outcome could correlate with particular antigen specificities of infused TIL. Results show that the infusion of Melan-A/MART-1 reactive TIL appears to be associated with a longer relapse-free survival for HLA-A2 patients. These results further support the relevance of Melan-A/MART-1 antigen as a prime target for immunotherapy protocols in melanoma.
癌症的过继性疗法大多是在晚期癌症患者中使用肿瘤浸润淋巴细胞（TIL）进行测试的。由于TIL的肿瘤特异性较差和/或肿瘤负荷较高，此前的结果令人沮丧，而最近的研究重申了这种疗法的巨大潜力，尤其是在黑色素瘤治疗方面。我们对88例III期黑色素瘤患者进行了一项II/III期随机试验，这些患者在肿瘤完全切除后接受了自体TIL加白细胞介素-2（IL-2）或仅接受IL-2治疗。我们之前报告了临床和免疫学结果，支持肿瘤反应性TIL输注能够预防黑色素瘤疾病的进一步发展，并提高仅一个肿瘤侵犯淋巴结患者的总生存率。总生存期和无病生存期与输注的肿瘤特异性TIL数量之间缺乏相关性，这表明治疗效果可能取决于其他参数，如TIL的抗原特异性、功能或持久性。在此，我们研究了输注到本试验所纳入患者体内的TIL对一组38种共享肿瘤相关抗原（TAA）的识别情况，以确定治疗结果是否与输注TIL的特定抗原特异性相关。结果显示，对于HLA-A2患者，输注Melan-A/MART-1反应性TIL似乎与更长的无复发生存期相关。这些结果进一步支持了Melan-A/MART-1抗原作为黑色素瘤免疫治疗方案主要靶点的相关性。
